Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding.
Axoneme
/ metabolism
Binding Sites
Cell Cycle Proteins
/ chemistry
Chlamydomonas reinhardtii
/ metabolism
Crystallography, X-Ray
Humans
Microfilament Proteins
/ chemistry
Microscopy, Fluorescence
Molecular Chaperones
/ chemistry
Multiprotein Complexes
/ chemistry
Mutation
Nuclear Proteins
/ chemistry
Phosphoproteins
/ chemistry
Protein Binding
Protein Conformation
Protein Domains
Single Molecule Imaging
Tubulin
/ metabolism
MEIG1
PACRG
PACRGL
Parkinson
axoneme
cilia
flagella
microtubule
sperm
tubulin
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
03 06 2021
03 06 2021
Historique:
received:
17
06
2020
revised:
16
12
2020
accepted:
08
01
2021
pubmed:
3
2
2021
medline:
14
1
2022
entrez:
2
2
2021
Statut:
ppublish
Résumé
The Parkin co-regulated gene protein (PACRG) binds at the inner junction between doublet microtubules of the axoneme, a structure found in flagella and cilia. PACRG binds to the adaptor protein meiosis expressed gene 1 (MEIG1), but how they bind to microtubules is unknown. Here, we report the crystal structure of human PACRG in complex with MEIG1. PACRG adopts a helical repeat fold with a loop that interacts with MEIG1. Using the structure of the axonemal doublet microtubule from the protozoan Chlamydomonas reinhardtii and single-molecule fluorescence microscopy, we propose that PACRG binds to microtubules while simultaneously recruiting free tubulin to catalyze formation of the inner junction. We show that the homologous PACRG-like protein also mediates dual tubulin interactions but does not bind MEIG1. Our findings establish a framework to assess the function of the PACRG family of proteins and MEIG1 in regulating axoneme assembly.
Identifiants
pubmed: 33529594
pii: S0969-2126(21)00001-0
doi: 10.1016/j.str.2021.01.001
pmc: PMC8178172
mid: NIHMS1664406
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
MEIG1 protein, human
0
Microfilament Proteins
0
Molecular Chaperones
0
Multiprotein Complexes
0
Nuclear Proteins
0
PACRG protein, human
0
Phosphoproteins
0
Tubulin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
572-586.e6Subventions
Organisme : NIGMS NIH HHS
ID : P30 GM124165
Pays : United States
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.-F.T. is the director of the Proteomics platform at the Research Institute of the McGill University Health Centre, as well as a member of the scientific advisory board of Mitokinin, Inc.
Références
Nature. 1998 Jan 8;391(6663):199-203
pubmed: 9428769
Mol Biol Evol. 2008 Sep;25(9):1909-21
pubmed: 18566020
Biol Reprod. 2006 Apr;74(4):751-9
pubmed: 16382026
Anal Biochem. 2019 Dec 1;586:113416
pubmed: 31499019
N Engl J Med. 2009 Dec 31;361(27):2609-18
pubmed: 20018961
Dev Biol. 2010 Feb 15;338(2):158-67
pubmed: 20004656
Methods Enzymol. 1991;196:478-85
pubmed: 2034137
Neurosci Lett. 2009 Aug 21;460(1):97-101
pubmed: 19463890
J Cell Sci. 2005 Dec 1;118(Pt 23):5421-30
pubmed: 16278296
Nat Biotechnol. 2004 Oct;22(10):1297-301
pubmed: 15378068
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Methods Cell Biol. 2010;95:221-45
pubmed: 20466138
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Cell Tissue Res. 1981;215(3):515-29
pubmed: 7214493
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15616-15624
pubmed: 31308240
Neuron. 2015 Jul 15;87(2):371-81
pubmed: 26182419
Nature. 2018 Sep;561(7722):258-262
pubmed: 30135585
Nature. 2013 Sep 26;501(7468):512-6
pubmed: 24005326
FEBS Lett. 2008 Apr 30;582(10):1413-8
pubmed: 18387367
Cell Mol Life Sci. 2019 Dec;76(23):4589-4611
pubmed: 31254044
Sci Rep. 2016 Jan 04;6:18278
pubmed: 26726850
Nature. 2004 Jul 8;430(6996):223-6
pubmed: 15241417
J Biol Chem. 2003 Dec 19;278(51):51901-10
pubmed: 14532270
Elife. 2020 Jan 17;9:
pubmed: 31951202
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R27-35
pubmed: 12668594
Cell. 2019 Oct 31;179(4):909-922.e12
pubmed: 31668805
Elife. 2017 Nov 10;6:
pubmed: 29125462
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11364-9
pubmed: 18687901
Mol Biol Cell. 2019 Jul 15;30(15):1805-1816
pubmed: 31116684
Nat Chem Biol. 2017 Dec;13(12):1253-1260
pubmed: 29035361
Nat Protoc. 2008;3(7):1171-9
pubmed: 18600222
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Nature. 2004 Feb 12;427(6975):636-40
pubmed: 14737177
Mol Cell. 2013 Mar 7;49(5):908-21
pubmed: 23453807
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Neurobiol Dis. 2007 Aug;27(2):238-47
pubmed: 17590346
Sci Rep. 2018 May 14;8(1):7528
pubmed: 29760428
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8402-7
pubmed: 15148410
Acta Biochim Biophys Sin (Shanghai). 2004 Feb;36(2):141-6
pubmed: 14970911
PLoS Negl Trop Dis. 2016 Feb 04;10(2):e0004412
pubmed: 26844546
Nature. 1998 Apr 9;392(6676):605-8
pubmed: 9560156
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4078-83
pubmed: 12642658
Dev Biol. 2016 Jan 1;409(1):55-71
pubmed: 26542012
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Cell Motil Cytoskeleton. 2007 Nov;64(11):814-21
pubmed: 17654607
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nat Rev Nephrol. 2019 Apr;15(4):199-219
pubmed: 30733609
Med Mol Morphol. 2017 Jun;50(2):59-67
pubmed: 27660208
Dev Cell. 2012 Jul 17;23(1):181-92
pubmed: 22727374
Sci Signal. 2020 Feb 04;13(617):
pubmed: 32019898
Curr Opin Cell Biol. 2019 Aug;59:73-80
pubmed: 31054512
Front Neurol. 2013 Apr 19;4:38
pubmed: 23626584
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17055-60
pubmed: 19805151
Curr Biol. 2011 May 24;21(10):805-14
pubmed: 21549602
Mol Biol Cell. 2016 Jul 1;27(13):2133-44
pubmed: 27193298
J Mol Biol. 2003 Feb 7;326(1):11-9
pubmed: 12547187
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Mol Cell Proteomics. 2002 Jun;1(6):451-65
pubmed: 12169685
Elife. 2018 Nov 06;7:
pubmed: 30398148
BMC Neurosci. 2007 Nov 28;8:102
pubmed: 18045479
Dev Cell. 2015 Nov 23;35(4):497-512
pubmed: 26585297
Development. 2015 Mar 1;142(5):921-30
pubmed: 25715396
J Biol Chem. 2003 Oct 31;278(44):43628-35
pubmed: 12930822
Proc Natl Acad Sci U S A. 2019 May 7;116(19):9370-9379
pubmed: 31004057
Nature. 2019 Jul;571(7766):565-569
pubmed: 31316206